Inborn errors of immunity manifesting as atopic disorders

• Published in: Journal of allergy and clinical immunology Vol. 148; no. 5; pp. 1130 - 1139
• Main Authors: Vaseghi-Shanjani, Maryam, Smith, Kelsey L., Sara, Rahnuma J., Modi, Bhavi P., Branch, Anna, Sharma, Mehul, Lu, Henry Y., James, Elliot L., Hildebrand, Kyla J., Biggs, Catherine M., Turvey, Stuart E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2021
• Subjects: allergy; Disease Management; Disease Susceptibility; Genetic Association Studies; Genetic Predisposition to Disease; genetics; Humans; Hypersensitivity, Immediate - diagnosis; Hypersensitivity, Immediate - epidemiology; Hypersensitivity, Immediate - etiology; Hypersensitivity, Immediate - therapy; Immunity - genetics; inborn errors of immunity; monogenic allergic diseases; monogenic atopy; Phenotype; Primary atopic disorders; primary immunodeficiencies; monogenic allergic diseases; DLBCL; Primary atopic disorders; ARPC1B; DOCK8; WAS; BCL10; IL-1R; MyD88; SCID; HIES; MALT1; CBM; WASP; genetics; ASCT2; TGF-β; HSCT; GOF; CADINS; GLUT1; SPINK5; Treg; ERBIN; allergy; IGF-1; IRAK4; IEI; monogenic atopy; ZAP70; PAD; STAT; primary immunodeficiencies; JAK; IPEX; inborn errors of immunity; mTORC1; CARD11; IL-4Rα
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2021.08.008

Inborn errors of immunity are traditionally best known for enhancing susceptibility to infections. However, allergic inflammation, among other types of immune dysregulation, occurs frequently in patients with inborn errors of immunity. As such, the term primary atopic disorders (PADs) was recently coined to describe the group of heritable monogenic allergic disorders. It is becoming increasingly important for clinicians to recognize that allergic diseases such as food allergy, atopic dermatitis, and allergic asthma are expressions of misdirected immunity, and in patients who present with severe, early-onset, or coexisting allergic conditions, these can be indications of an underlying PAD. Identifying monogenic allergic disease through next-generation sequencing can dramatically improve outcomes by allowing the use of precision-based therapy targeting the patient’s underlying molecular defect. It is therefore imperative that clinicians recognize PADs to be able to provide informed therapeutic options and improve patient outcomes. Here, we summarize the clinical features commonly seen with each of the currently known PADs, identify clinical warning signs that warrant assessment for PADs, and lastly, discuss the benefits of timely diagnosis and management of these conditions.